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مژده احمدی، مهدی زوار

Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumorfree conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model. Our results indicate that Foxp3 vaccination continuously reduces Treg population in both the tumor site and the spleen. Surprisingly, Treg reduction was associated with a significant decrease in the frequency of MDSC, both in the spleen and in the tumor environment. Furthermore, Foxp3 vaccination resulted in a significant reduction of arginase1(Arg-1)-induced nitric oxide synthase (iNOS), reactive oxygen species (ROS) and suppressed MDSC activity. Moreover, this concurrent depletion restored production of inflammatory cytokine IFN-γ and enhanced tumor-specific CTL response, which subsequently resulted in the reduction of tumor growth and the improved survival rate of vaccinated mice. In conclusion, our results revealed that Foxp3 vaccine promotes an immune response against tumor by targeting both Treg and MDSC, which could be exploited as a potential immunotherapy approach.

Regulatory T cells, Myeloid-derived suppressor cells, Foxp3, Melanoma

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احمدی، مژده، زوار، مهدی، 1404، واکسن پیشگیرانه DNA که سلول های T تنظیمی Foxp3+ را هدف قرار می دهد، سلول های سرکوبگر مشتق از میلوئید را کاهش می دهد و پاسخ های ایمنی ضد ملانوم را در مدل موش بهبود می بخشد.، کنگره بین المللی زیست پزشکی سرطان و سلولهای بنیادی، http://conf.sums.ac.ir/fa/archive_index.php?c=HN-icsbc1&aid=1514185